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by
Sanjit K. Roy |
Total Records (
2 ) for
Sanjit K. Roy |
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Padmaja Gade
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Sanjit K. Roy
,
Hui Li
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Shreeram C. Nallar
and
Dhananjaya V. Kalvakolanu
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Transcription factor C/EBP-β regulates a number of physiological responses. During an investigation of the growth-suppressive effects of interferons (IFNs), we noticed that cebpb–/– cells fail to undergo apoptosis upon gamma IFN (IFN-γ) treatment, compared to wild-type controls. To examine the basis for this response, we have performed gene expression profiling of isogenic wild-type and cebpb–/– bone marrow macrophages and identified a number of IFN-γ-regulated genes that are dependent on C/EBP-β for their expression. These genes are distinct from those regulated by the JAK-STAT pathways. Genes identified in this screen appear to participate in various cellular pathways. Thus, we identify a new pathway through which the IFNs exert their effects on cellular genes through C/EBP-β. One of these genes is death-associated protein kinase 1 (dapk1). DAPK1 is critical for regulating the cell cycle, apoptosis, and metastasis. Using site-directed mutagenesis, RNA interference, and chromatin immunoprecipitation assays, we show that C/EBP-β binds to the promoter of dapk1 and is required for the regulation of dapk1. Both mouse dapk1 and human dapk1 exhibited similar dependences on C/EBP-β for their expression. The expression of the other members of the DAPK family occurred independently of C/EBP-β. Members of the C/EBP family of transcription factors other than C/EBP-β did not significantly affect dapk1 expression. We identified two elements in this promoter that respond to C/EBP-β. One of these is a consensus C/EBP-β-binding site that constitutively binds to C/EBP-β. The other element exhibits homology to the cyclic AMP response element/activating transcription factor binding sites. C/EBP-β binds to this site in an IFN-γ-dependent manner. Inhibition of ERK1/2 or mutation of an ERK1/2 site in the C/EBP-β protein suppressed the IFN-γ-induced response of this promoter. Together, our data show a critical role for C/EBP-β in a novel IFN-induced cell growth-suppressive pathway via DAPK1. |
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Rishipal R. Bansode
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Wei Huang
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Sanjit K. Roy
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Madhu Mehta
and
Kamal D. Mehta
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Metabolic syndrome is common in the general population, butthere is little information available on the underlying signalingmechanisms regulating triglyceride (TG) content in the body.In the current study, we have uncovered a role for protein kinaseCβ (PKCβ) in TG homeostasis by studying the consequencesof a targeted disruption of this kinase. PKCβ-/- mutantmice were considerably leaner and the size of white fat depotswas markedly decreased compared with wild-type littermates.TG content in the liver and skeletal muscle of PKCβ-/-mice was also significantly low. Interestingly, mutant animalswere hyperphagic and exhibited higher food intake and reducedfeed efficiency versus wild type. The protection from obesityinvolves elevated oxygen consumption/energy expenditure andincreased fatty acid oxidation in adipose tissue with concurrentincreased mitochondria genesis, up-regulation of PGC-1α and UCP-2,and down-regulation of perilipin. The ability of PKCβ deficiencyto promote fat burning in adipocytes may suggest novel therapeuticstrategies for obesity and obesity-related disorders. |
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